Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse

Hyeon Seok Son,Insung Ahn,Byeong-Jin Jeong

doi:10.3858/emm.2009.41.10.081

Abstract

Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.

Highlights

Coronaviruses (CoVs) which are included in the family Coronaviridae are enveloped and contain the largest RNA genomes with some reaching almost 30,000 nucleotides (Dimmock et al, 2002)
Among the CoV genes, the first two principal components of nucleocapsd genes accounted for 57.6% and 34.2%, whereas those of spike genes accounted for 60.8% and 27.8% of the total variance of the data set, respectively (Figure 1A and 1B)
Codon usage bias has been studied in various organisms ranging from virus to eukaryote, and optimized codon usages in the target viral genes have been made to improve the efficacy of DNA vaccines development (Ramakrishna et al, 2004; Shackelton et al, 2006; van Hemert et al, 2007; Wang et al, 2006a, 2006b)

Summary

Introduction

Coronaviruses (CoVs) which are included in the family Coronaviridae are enveloped and contain the largest RNA genomes with some reaching almost 30,000 nucleotides (Dimmock et al, 2002). They primarily infect the upper respiratory and gastrointestinal tract of animals, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly emerged group 2 CoV, spread rapidly from Asia to North America and Europe with a high degree of transmissibility and mortality (Lew et al, 2003; Riley et al, 2003; Friman et al, 2008). These cDNA fragments are inserted into a bacterial DNA vaccine plasmid such as escherichia coli plasmid, and lately, the prepared DNA vaccine is injected into the cells of the target organisms such as mouse, rabbit or human subjects to produce one or more specific proteins by mimicking viral replication and protein produc-

Methods

Results

Conclusion